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从成年小鼠大脑中纯化神经前体细胞:全面的基因表达分析为细胞迁移、分化和稳态调控提供了新见解。

Purification of neuronal precursors from the adult mouse brain: comprehensive gene expression analysis provides new insights into the control of cell migration, differentiation, and homeostasis.

作者信息

Pennartz Sandra, Belvindrah Richard, Tomiuk Stefan, Zimmer Céline, Hofmann Kay, Conradt Marcus, Bosio Andreas, Cremer Harold

机构信息

Memorec Biotec GmbH, a Miltenyi Biotec Company, 50829 Cologne, Germany.

出版信息

Mol Cell Neurosci. 2004 Apr;25(4):692-706. doi: 10.1016/j.mcn.2003.12.011.

Abstract

The progeny of neural stem cells in the subventricular zone (SVZ) of the adult mammalian brain consists in polysialylated NCAM-expressing immature neurons (PSA(+) cells), which migrate to the olfactory bulb (OB) to differentiate into GABAergic interneurons. We purified murine PSA(+) cells directly from the adult brain by FACS and analyzed their gene expression profile by SAGE. Comparative analyses led to the identification of precursor-enriched genes, including Survivin, Sox-4, Meis2, Dishevelled-2, C3aR1 and Riken 3110003A17, and many so far uncharacterized transcripts. Cluster analysis showed that groups of genes involved in axon guidance and gene clusters implicated in chemotaxis are strongly upregulated, indicating a role of both cues in the control of cell migration in the adult brain. Furthermore, genes involved in apoptosis and cell proliferation are co-expressed, suggesting that the amount of precursors that is present in the adult brain is a result of an equilibrium of these processes.

摘要

成年哺乳动物脑室内下区(SVZ)神经干细胞的子代包含表达多唾液酸神经细胞黏附分子(PSA(+)细胞)的未成熟神经元,这些细胞迁移至嗅球(OB)并分化为γ-氨基丁酸能中间神经元。我们通过荧光激活细胞分选术(FACS)直接从成年小鼠脑中纯化出PSA(+)细胞,并利用基因表达序列分析(SAGE)对其基因表达谱进行分析。比较分析鉴定出了富含前体细胞的基因,包括生存素(Survivin)、Sox-4、Meis2、散乱蛋白2(Dishevelled-2)、C3aR1和RIKEN 3110003A17,以及许多迄今未被表征的转录本。聚类分析表明,参与轴突导向的基因群以及与趋化作用相关的基因簇均显著上调,这表明这些信号在成年脑的细胞迁移控制中均发挥作用。此外,参与细胞凋亡和细胞增殖的基因共同表达,这表明成年脑中前体细胞的数量是这些过程平衡的结果。

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